Both coronary artery disease and influenza outbreaks contribute significantly to worldwide morbidity and mortality. An increasing number of epidemiologic studies have concluded that a temporal association exists between acute viral illnesses and myocardial infarction. Viral illnesses such as influenza can cause or exacerbate coronary atherosclerosis by activating inflammatory pathways. Data from a large case-controlled trial and two randomized controlled trials suggest that influenza vaccination in patients with coronary artery disease may lead to a decrease in incidence, morbidity, and mortality from acute myocardial infarction. A meta-analysis of the two randomized controlled trials for cardiovascular death demonstrated a pooled relative risk of 0.39 (95% confidence interval, 0.20-0.77) for patients who received the influenza vaccine compared with placebo.